Characteristics, Risk Factors, and Outcomes in Acute Kidney Injury Patients: A Retrospective Cross-Sectional Study, Palestine

Background Acute kidney injury (AKI) is a major medical problem affecting patients' quality of life and healthcare costs. Objectives This study evaluated the severity, risk factors, and outcomes of patients diagnosed with acute kidney injury (AKI), including community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI), who were admitted to tertiary institutions in Palestine. Methods This retrospective cross-sectional study was conducted at multiple tertiary care hospitals in Palestine by reviewing patient charts from January 2020 to March 2023. The study included all patients aged ≥18 years who were admitted to the hospital and diagnosed with AKI at admission (CA-AKI) or who developed AKI 48 hours after admission (HA-AKI). Patients with incomplete medical records and those with no reported creatinine levels during their stay, pregnant women, kidney transplant patients, and end-stage renal disease patients were excluded. Data were analyzed using SPSS v22.0. The incidence of AKI in each group was compared using the chi-squared test. Results This study included 259 participants. HA-AKI was present in 27.3% of the patients, while CA-AKI was 72.7%. The most common stage among patients was stage 3 (55.7%, HA-AKI) (42.9%, CA-AKI), and the most common comorbidity contributing to AKI was CKD. NSAIDs, ACE-I/ARBs, and DIURETICs were the most nephrotoxic drugs contributing to AKI. Patients with hyperphosphatemia, hyperkalemia, severe metabolic acidosis, or stage 3 AKI require renal replacement therapy. In addition, our findings revealed a significant association among AKI mortality, age, and heart disease. Conclusion CA-AKI was more prevalent than HA-AKI in Palestinian patients admitted for AKI. Risk factors for AKI included diabetes, CKD, and medications (antibiotics, NSAID, diuretics, and ACE-I/ARB). Preventive measures, medication management, and disease state management are necessary to minimize AKI during hospital admission or in the community.


Introduction
AKI is a life-threatening syndrome that may lead to serious long-term complications such as chronic kidney disease or progression to end-stage renal disease.It afects more than 13 million people annually, resulting in 1.7 million deaths, afecting 1 in 5 hospitalized patients, and reaching up to 50% of critically ill patients [1,2].Furthermore, more than 50% of patients transferred to the intensive care unit (ICU) develop acute renal impairment during their frst transfer hours [1,[3][4][5].AKI is associated with increased healthcare costs and length of hospital stay [6].Terefore, strategies for detecting, preventing, and facilitating kidney recovery are required.
Acute kidney injury (AKI) is a sudden loss of kidney function that results in the retention of urea and other nitrogenous waste products, causing an imbalance of plasma fuid and electrolytes [3,7].Kidney Disease Improving Global Outcomes (KDIGOs) classify kidney injury into three stages based on serum creatinine levels and urine output [4].Furthermore, AKI can be classifed based on its etiology as prerenal, intrinsic, or postrenal [5].
Risk factors for AKI have been well documented in the literature, including age, diabetes, cardiovascular disease, chronic kidney disease, and nephrotoxic medications [8,9].Diabetes being the most common risk factor account for 50% of patients with AKI.Patients with heart failure have a 26% risk of developing AKI compared with 14% in those without heart failure [10].Te incidence of AKI in patients diagnosed with sepsis ranges from 11% to 70% [11].Moreover, obstructive nephropathy may have a 5-10% impact on AKI [12].Many commonly prescribed medications have been linked up to 50% increase in the risk of AKI, especially nephrotoxic drugs when used in combinations such as renin-angiotensin system inhibitors, diuretics, nonsteroidal anti-infammatory drugs (NSAIDs), aminoglycosides, vancomycin, and radiocontrast agents [13][14][15].
Diferences in the etiology, risk factors, and prevalence of community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI) have been reported in diferent regions worldwide [16,17].Communityacquired AKI (CA-AKI) has been reported as the dominant form of AKI [18].Both types are associated with diferent risk factors, presentation, and epidemiological profles.Furthermore, controversial reports on prognoses, mortality rates, renal complications, length of hospital stay, and healthcare costs have been published [1,19].In a study conducted in the United Kingdom, CA-AKI was more severe than HA-AKI, although both had similar risk factors.CA-AKI patients had lower mortality rates despite having risk factors similar to those of patients with HA-AKI; furthermore, patients with CA-AKI had better survival rates and shorter hospital stays [20].Furthermore, in a meta-analysis, CA-AKI patients had a good prognosis and improved clinical manifestations with fewer reported ICU admissions, hospital stays, and mortality rates [21].It has been reported in the literature that AKI features and outcomes difer by geographic and socioeconomic regions [22].
Regional studies on AKI prevalence, risk factors, and settings are limited.A recent study in Turkey revealed that nephrotoxic drugs are the most common etiology of AKI with a 24% death rate after 6 months of diagnosis, and a study in Saudi Arabia on HA-AKI reported serious complications and minimal renal recovery [23,24].To the best of our knowledge, no studies have been conducted in Palestine to explore this topic; therefore, this study aimed to evaluate the severity, risk factors, outcomes, and prevalence of CA-AKI and HA-AKI in patients diagnosed with AKI at tertiary care hospitals in Palestine.Te fndings of this study will be used to establish preventive measures to ensure patient safety, optimize medication therapy, and prevent complications.

Study Design and Population.
Tis retrospective crosssectional study was conducted at multiple tertiary care hospitals in Palestine by reviewing the patient data from January 2020 to March 2023.Te study included all patients aged ≥18 years who were admitted to the hospital and diagnosed with AKI at admission (CA-AKI) or who developed AKI 48 hours after admission (HA-AKI).Patients with incomplete medical records, those lacking reported creatinine levels during their stay, pregnant women, kidney transplant patients, or end-stage renal disease patients were excluded.

Data Collection.
Te data collection form was based on a review of other AKI studies.Data were gathered from patient records and entered into Google form sheets. Tis form was divided into fve sections.In the frst section, patient demographics, age, gender, social history, and admission, and discharge dates were recorded.Te second section included past medical history (acute and chronic medical conditions), and the third section included AKIrelated information, medications before and during admission, nephrotoxic drug exposure, and date of AKI diagnosis.Te fourth section included laboratory data (serum creatinine level and BUN ratio), stage categories (stages 1, 2, and 3), and AKI classifcation (prerenal, intrinsic, and postrenal).Te last section included AKI complications, metabolic acidosis, electrolyte imbalance, critical care admission, and mortality.

AKI Classifcation.
According to the Kidney Disease Improving Global Outcomes (KDIGO) approach, the patient population was divided into three stages depending on the serum creatinine level and urine output.Stage 1 is defned as an increase in SCr of less than 0.3 mg/dL within 48 hours or 1.5 to 1.9 times baseline SCr within 7 days.Stage 2 shows an increase in SCr of 2.0 to 2.9 over the baseline SCr.Stage 3 is defned as an increase in SCr of more than 3.0 times the baseline, an increase in SCr of more than 4.0 mg/dL, or the start of renal replacement therapy despite having previously reached a KDIGO stage.

Statistical Analysis.
Data were analyzed using SPSS v22.0.Te data were imported, cleaned, and recorded as needed.Continuous variables are presented as mean ± SD or median (25th-75th percentile), as appropriate.Categorical variables were presented as proportions.Pearson's chisquare test and Fischer's exact test were performed to compare the CA-AKI and HA-AKI groups and to assess the diferences in complications.For signifcant results, binary logistic regression (the entered model) was performed to identify confounders.Odds ratios (ORs) with 95% confdence intervals (CIs) were also calculated.Te hypotheses were two-tailed, and a P value less than 0.05 was considered statistically signifcant.Te diagnoses on admission are presented in Figure 1.Te most common diagnosis for patients with AKI on admission was renal disease (52.9%), followed by cardiovascular (23.2%) and pulmonary (21.9%) diseases; infections were the least common diagnoses (1.2%).

Ethical
A total of 189 participants (72.7%) were admitted to the hospital with AKI (CA-AKI), whereas 70 (27.3%)developed AKI during hospitalization (HA-AKI).Demographic differences between the CA-AKI and HA-AKI groups are shown in Table 1.Tere was no signifcant diference in the possibility of developing CA-AKI or HA-AKI and patients' age, gender, or AKI stage.Prerenal etiology was signifcantly more common among CA-AKI patients (54.5%) than HA-AKI patients (41.4%) (P � 0.006).A comparison of various comorbidities in patients with HA-AKI and CA-AKI revealed a signifcantly higher prevalence of CKD in patients with CA-AKI (32.3%) than in those with HA-AKI (11.4%;P � 0.001).No diference was found in the proportions of patients with diabetes mellitus, anemia, liver disease, or heart disease between the two groups.

Recovery.
Te proportions of patients recovering from baseline serum creatinine levels, persistent AKI, and renal replacement therapy did not difer between the CA-AKI and HA-AKI groups.ICU transfer frequency was signifcantly higher in the HA-AKI group (37.1%) than in the CA-AKI group (18.5%,P � 0.002).
Binary logistic regression results, presented in Table 2, revealed that among patients with AKI, increasing age and heart disease were two factors associated with an increased risk of mortality (P ≤ 0.001 and P � 0.003, respectively).A one-year increase in age was associated with an approximately 6% increase in mortality risk.Additionally, the risk of mortality increases by 70% in patients with heart disease.No diference in the risk of mortality was assessed between patients with other comorbidities, those who developed diferent complications, or those with diferent AKI stages.
As shown in Table 3, binary logistic regression analysis revealed a signifcant association between renal replacement therapy and AKI complications, including hyperphosphatemia and metabolic acidosis (P � 0.045 and P < 0.016, respectively).Patients who develop hyperkalemia or metabolic acidosis are at a higher risk of undergoing renal replacement therapy, by 68% and 82%, respectively.Furthermore, signifcant associations were found between renal replacement therapy and stage 3 diagnosis (P � 0.019); patients diagnosed with stage 3 disease were at a 38-fold higher risk of receiving renal replacement therapy.Te results revealed that a one-unit increase in baseline SrCr levels was associated with a two-fold increase in the risk of transfer to HD.

Discussion
In this study, we explored essential data and new information regarding AKI diagnosis, prevalence, patient characteristics, AKI settings (HA-AKI and CA-AKI), and complications.Several factors, including age and diseases such as diabetes, CKD, low blood pressure, and heart disease, as well as taking some medications, contribute to AKI [25].

Patient Characteristics.
In this study, CA-AKI was predominant compared with HA-AKI, although both shared similar risk factors and patient characteristics, including age, sex, stage, and comorbidities, with no signifcant diferences.A higher prevalence of CA-AKI has been reported in many developing countries, and a similar fnding was reported in a large Taiwanese adult retrospective cohort study [18,26,27].Te median age of patients diagnosed with AKI was 65 years.Furthermore, studies have shown that the risk of developing acute renal failure is three times higher in patients aged >65 years than in younger patients [28].Increased age has been reported as a risk factor in AKI patients because of the physiological and structural changes in the kidneys with aging, which reduce nephron mass and glomerular fltration rate with an increased tendency towards cellular apoptosis [29].Te results showed a strong association between age and mortality (P < 0.001).It is widely recognized that the elderly have a higher incidence of AKI, poor prognosis, and a higher mortality risk than other age groups.Elderly patients have frequent comorbidities, Te Scientifc World Journal

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Te Scientifc World Journal including diabetes, hypertension, and heart failure, and take many drugs; this can be associated with the severity and complexity of their condition and mortality [30,31].Te physiological changes related to age require caution in medication use and dosage and more frequent monitoring of efcacy and toxicity.Furthermore, tools have been established to ensure appropriate prescribing for the elderly that should be incorporated into clinical practice, such as the BEERS list, which includes medication doses that need to be reduced or medications that should be avoided in the elderly [32].
Among the 259 patients who developed AKI, 54.4% were male, and there was no relationship between gender and either CA-AKI or HA-AKI.Some studies have reported the presence and development of AKI in males due to the presence of androgens, which are essential factors that contribute to the destruction and disruption of kidney function by disrupting hemodynamics, which can be due to the more resistant eferent arterioles.In females, during the menstrual cycle, estrogen acts as a protective and therapeutic agent for the kidneys; however, this short-term efect decreases with age [29].Furthermore, in a recent Systematic Review and Meta-Analysis, male gender was one of the many risk factors that placed COVID-19 patients at greater risk of developing AKI (OR: 1.74 (1.47, 2.05), P < 0.05) [33].

Comorbidities.
In this study, there was no association between comorbidities such as diabetes, heart disease, liver disease, and anemia and the incidence of CA-AKI or HA-AKI, and patients with these comorbidities were more likely to develop AKI [34].A very similar fnding was illustrated in a Moroccan study where various comorbid conditions had equal prevalence among patients with CA-AKI and HA-AKI [35].Furthermore, patients with CKD are at an increased risk of developing AKI, which is signifcant in CA-AKI.In CKD patients, the kidney loses its response or tolerates stress such as infection, dehydration, nephrotoxic drugs, and comorbidities, which decreases the threshold for developing AKI afecting renal function or perfusion [36,37].In this study, CKD was a risk factor for CA-AKI, and in this study, it was clear that patients in the community setting have signifcant exposure to nephrotoxic medications, which calls for an increase in awareness of factors that might cause exacerbation of renal function.Te Scientifc World Journal

AKI Stage
AKI stage is a determining factor of prognosis, with the higher stage having a poorer outcome, stage 1 treated in primary care, and stage 3 treated in secondary care [38].In this study, stage 3 was the predominant stage regardless of the AKI setting, with approximately 50% of the participants having stage 3 AKI.A similar fnding was reported in a Sudanese study, and a smaller rate was reported in Chinese studies [39,40].Tis alarming fnding may explain the poor prognosis, poor outcomes, and extended length of hospital stay.Te late-stage presentation may be due to lack of access to care, lack of follow-up, understanding of AKI, and asymptomatic patients.Terefore, educating at-risk patients on the signs, symptoms, and aggravating factors of AKI is of utmost importance.Furthermore, detailed patient assessments and physical examinations when suspecting acute renal insufciency will promptly identify and treat the causes [41].

AKI Etiology.
Prerenal was the most prevalent etiology in the sample; almost half of the patients had prerenal AKI, which was signifcantly higher in the CA-AKI group.A similar fnding in a prospective study in a tertiary care center in China found that prerenal was the most frequent cause of AKI, occurring in 27.7% of the cases [42].Researchers in a recent regional study in Turkey that included 776 patients diagnosed with AKI found that prerenal AKI was the most prevalent etiology with high exposure to nephrotoxic medication, similar to our fnding [24].Prerenal AKI occurs due to kidney hypoperfusion, which can be related to a decline in cardiac output volume and renal perfusion due to diferent conditions such as bleeding, severe vomiting or diarrhea, dehydration, or diuretic use.Tis fnding can also be explained by the signifcantly higher exposure to nephrotoxic drugs such as NSAIDs, ACE-I/ARBs, and diuretics in the CA-AKI group.A very similar fnding was also reported in a Taiwanese study [18].In prerenal AKI, many changes occur in the aferent and eferent arterioles due to the use of diferent drugs, such as ACE inhibitors or ARBs, which decrease eferent arteriolar resistance.Nonsteroidal anti-infammatory drugs (NSAIDs) afect the renal production of prostaglandin and cause vasodilation of the aferent arterioles, which generally need to be constricted [43].

Nephrotoxic Drugs.
Te drug classes associated with AKI in this study were similar to those reported previously.Tis fnding is very similar to a study conducted in China, where the prevalence of nephrotoxic drugs was 57% and much higher in Taiwan [44,45].Evidence suggests that exposure to at least one nephrotoxic drug is associated with AKI and its severity [46].
ACE-I is one of the most efective drugs for the management of many comorbid diseases such as hypertension and congestive heart failure.However, appropriate dosage and monitoring at initiation and during treatment are essential to prevent complications.ACE-I/ARBS alters the glomerular fltration rate, afects interglomerular hemodynamics, and causes AKI [47].NSAIDs are widely used as over-the-counter (OTC) medications.Surprisingly, NSAIDs, which are contraindicated in patients with AKI, are frequently used in patients with AKI during admission.In a regional cohort study in Saudi Arabia, NSAIDs were the most common cause of in-hospital AKI [48].NSAIDs can cause a poor prognosis, mainly when used with other medications such as ACE and diuretics during AKI [49].A recent study in Palestine among college students reported very high use of NSAID and suggested increasing awareness of adverse efects associated with NSAID [50].
ACE-I, ARB, and NSAIDs have a nephrotoxic efect on vasodilation of the eferent arteriolar and vasoconstriction of the aferent renal arteriolar, respectively [47].A national cohort study showed that ICU survivors exposed to at least one nephrotoxic agent needed renal replacement therapy [30].
Antibiotics were signifcantly associated with HA-AKI during hospitalization.Tis fnding is in line with other reports in the literature, where antibiotics induce renal toxicity through diferent mechanisms that alter intraglomerular hemodynamics or cause infammatory changes in the renal tubules [8,51].Cephalosporin, aminoglycoside, bacitracin, and vancomycin are associated with an increase in the risk of acute kidney injury (AKI) [52].Medication management and appropriate renal dosing and monitoring, especially in patients with multiple comorbidities and multiple medications that afect renal function, are essential to prevent AKI and reduce hospital stay.

AKI Outcomes.
Te outcomes of AKI management include recovery to baseline, the need for RRT, ICU transfer, and mortality.In this study, HA-AKI patients had a signifcantly higher ICU transfer rate than CA-AKI patients did.A similar fnding was reported in a regional multicenter Egyptian cohort study conducted in four teaching hospitals in Alexandria, where 39.6% of patients with AKI were referred to intensive care [53].On the other hand, a study in Pakistan revealed higher mortality among CA-AKI patients [54].
Te mortality rates in this study signifcantly increased with age and in the patients diagnosed with heart disease.Interrelations between the kidney and the heart are well recognized, and under normal circumstances, any dysfunction in one organ will cause another to compensate and maintain adequate perfusion in the body; however, in renal or heart disease, there is a dysfunction in this feedback mechanism leading to negative outcomes and poor prognosis; therefore, it has been reported that an increase in serum creatine will negatively afect the prognosis of heart failure [55].
A similar retrospective study was conducted at a tertiary teaching hospital in the Khartoum Study.Osman et al. reported lower overall mortality rates with higher mortality rates associated with age, liver disease, and sepsis [39].
Te Improving Global Outcomes (KDIGO) guidelines classify AKI according to the severity of kidney damage in three stages.As the stage increases, the severity increases, the risk of developing acid-base and electrolyte imbalances increases, and the need for RRT, which was evident in this study, hyperkalemia, hyperphosphatemia, and metabolic acidosis was signifcantly associated with the need for RRT [43,56].Metabolic acidosis has systemic efects that disrupt cellular and organ function and lead to adverse complications of AKI, as reported by many studies [57][58][59].Electrolyte disturbances, such as hyperkalemia, hypermagnesemia, and metabolic acidosis, were signifcantly associated with higher mortality rates.Patients with hyperkalemia have renal tubular abnormalities and severe stages; furthermore, hyperkalemia increases the risk of arrhythmias, increasing the risk of mortality [60,61].
Hyperkalemia is highly associated with abnormalities in electrocardiograms (ECG) and arrhythmias.Furthermore, hyperphosphatemia increases the risk of secondary hyperthyroidism and cardiovascular calcination; prompt treatment is essential and lifesaving [62,63].Severe metabolic acidosis can afect the cardiovascular system, making it a crucial indicator for starting RRT [64].Te STARRT-AKI study, which involved 3019 patients from diferent countries, focused on the outcome of early initiation of RRT in stages 2 and 3 of AKI and found that early initiation of therapy did not afect the mortality rate.In this study, 30.8% of stage 3 patients need emergency RRT, and the mortality rate was higher among these patients, as illustrated by the START study that signifcantly ill patients might not have a reduced mortality rate when undergoing dialysis [65].

Limitations/Strength
Tis is the frst study performed in multiple hospitals in Palestine and can serve as a core study for future research in this feld.AKI was assessed using the Kidney Disease Improving Global Outcome (KIDGO) guidelines.Tis study provides information on the occurrence of AKI in diferent settings (hospital vs. community) and is the frst to compare the diferences between CA-AKI and HA-AKI patients in Palestine.In addition, information on the outcomes (dialysis or mortality) of acute renal impairment was also collected.Tis study has several limitations, including a small sample size and limited generalization of the results.Te study's retrospective design has limitations: retrospective studies only established an association, not a direct cause-efect relationship with risk factors and outcome, and data were collected from medical charts, where patients with missing information or documentation that could afect the results were excluded.Furthermore, neither the healthcare provider nor the patient was contacted, and information was only obtained from medical charts.Tis calls for prospective and interventional long-term studies to further explore AKI risk factors, etiology prevention, and management in Palestine.

. Conclusion
In this study, we explored the factors associated with AKI.CA-AKI was more prevalent than HA-AKI in Palestinian patients diagnosed with AKI at a tertiary care hospital in Palestine.Nephrotoxic medications (antibiotics, NSAID, diuretics, and ACE-I/ARB) were signifcant risk factors for AKI.Mortality rates increase with age in patients with congestive heart failure.Stage 3 and prerenal etiology were the most common presentations.Te fndings of this study highlight Te Scientifc World Journal the need to take appropriate measures to increase awareness among patients and healthcare providers of risk factors associated with kidney injury in a community or hospital setting.Te healthcare system in Palestine faces many challenges due to the lack of resources, such as hospital beds and dialysis units, adding more stress and responsibilities to healthcare providers; therefore, a thorough patient evaluation for early diagnosis and detection of AKI during admission or ofce visits, addressing modifable risk factors for AKI, lead to an early intervention to prevent complications, adverse outcomes, hospital stay, and admission.Furthermore, the community pharmacist, also available in the community and serving as a healthcare provider in medication management, is responsible for ensuring the appropriate use of commonly prescribed and utilized nephrotoxic medications to decrease drug-induced AKI.

Table 2 :
Determinants of mortality in patients with acute kidney injury.

Table 3 :
Determinants of the association between patient characteristics and need for renal replacement therapy.